Prostaglandins are synthetized by cerebral vessels and tissues and have vasoactive effects. Their role in control of cerebral blood (CBF), however, is controversial. We propose to examine systematically the role played by prostaglandins in control of the cerebral circulation. Studies are designed to determine whether prostaglandins are involved in maintenance of resting CBF and in cerebrovascular dilatation during hypercapnia, and whether prostaglandins limit constrictor effects of sympathetic nerves on cerebral arteries. several new approaches will be used. First, regional and total CBF will be measured with microspheres. Second, CBF will be measured continuously using a new method developed recently by the applicant. Cerebral blood flow is determined from measurements of diameter and blood velocity in pial artery. Third, efficacy and specificity of inhibition of prostaglandin synthesis in cerebral arteries and tissues by cyclooxygenase inhibitors will be examined using the cranial window method. An added feature of these studies is that experiments will be performed on awake animals when possible. It is expected that administration of cyclooxygenase inhibitors will not afect CBF during normocapnia dn hypercapnia in awake rabbits. Due to species differences, however, prostaglandins may contribute to regulation of CBF under these conditions in awake rats. In other studies, it is expected tht inhibition of prostaglandin synthesis will unmask constrictor effects of smpathetic nerves on CBF. These studies will provide new information on regulation of CBF.